Literature Review

Sodium Oxybate Reduces Daytime Sleepiness in Parkinson’s Disease

Researchers say that their sample size is insufficient to support conclusions about the treatment’s safety.


 

Sodium oxybate effectively treats excessive daytime sleepiness and nocturnal sleep disturbance in patients with Parkinson’s disease, according to research published in the January issue of JAMA Neurology. Patients receiving this therapy should be monitored with follow-up polysomnography to rule out treatment-related complications, the investigators said.

Many patients with Parkinson’s disease have excessive daytime sleepiness and disturbed sleep, but few treatments are available for them. An open-label study found that sodium oxybate, a first-line therapy for narcolepsy type 1, improved sleep and reduced daytime sleepiness in Parkinson’s disease.

A Phase II Crossover Study

To investigate this treatment further, Christian Baumann, MD, Senior Physician at University Hospital Zürich, and colleagues enrolled 18 patients into a double-blind, placebo-controlled, crossover phase IIa study. Eligible participants had Parkinson’s disease and regularly took dopaminergic medication. People with sleep apnea, cognitive problems, or depression, and those who took hypnotics, were excluded from the study.

Christian Baumann, MD

The researchers randomized participants in equal groups to sodium oxybate or placebo. Study medications were taken daily at bedtime and 2.5 to four hours later for six weeks. Doses were titrated between 3 g/night and 9 g/night according to efficacy and tolerability. After a two- to four-week washout period, participants crossed over to the opposite treatment arm for six weeks.

The trial’s primary efficacy end point was treatment effect on mean sleep latency (MSL), as measured by the Multiple Sleep Latency Test (MSLT). Secondary end points included change in subjective excessive daytime sleepiness (as measured by the Epworth Sleepiness Scale [ESS]), sleep quality, and objective sleep parameters. The investigators measured outcomes in the sleep laboratory at baseline and after six weeks of therapy.

Adverse Events Were Mild or Moderate

Five patients were excluded because of sleep apnea, and one patient withdrew consent. Of the 12 patients randomized, two were women. At baseline, participants’ mean age was 62, and mean disease duration was 8.4 years. Two patients developed de novo sleep apnea during sodium oxybate treatment, and one of them dropped out.

In the intention-to-treat analysis, sodium oxybate increased MSL by 2.9 minutes and reduced ESS score by 4.2 points. In the per-protocol analysis, sodium oxybate increased MSL by 3.5 minutes and reduced ESS score by 5.2 points. The responder rate for sodium oxybate (ie, the percentage of patients who had an improvement in MSL of more than 50%) was 67%. ESS score normalized for half of patients.

Every patient who received sodium oxybate had adverse events of mild or moderate intensity. The majority of these adverse events resolved after dose adjustment. Four patients continued to have adverse events until the end of the study, but none dropped out because of them.

Sodium oxybate had a treatment effect “that, to our knowledge, is unmatched by any other intervention reported so far,” said Dr. Baumann and colleagues. Although the sample size was large enough to provide class I evidence of efficacy, it was insufficient to support conclusions about safety, said the researchers. Larger follow-up trials thus are necessary, they concluded.

—Erik Greb

Suggested Reading

Büchele F, Hackius M, Schreglmann SR, et al. Sodium oxybate for excessive daytime sleepiness and sleep disturbance in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2018;75(1):114-118.

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